Strep Bacteria a Deadly Participant in Development of Colorectal Cancer

Colorectal cancer — cancer of the colon or rectum — is the third most commonly diagnosed cancer in the US. To reduce the chances of a diagnosis we are all urged to stop smoking, keep our weight down, decrease our intake of alcohol and red meat, keep active, and get screened for colon cancer. But, new research has found something that participates in the development of colorectal cancer that might not be as easy to control: A strep bacteria that promotes tumor growth.

Scientists and doctors have noted for years that patients with a particular strep bacterial infection often had colorectal cancer. But they didn't know if the bacteria caused cancer or the bacteria just liked to grow in the environment provided by the tumor cells.

Ritesh Kumar and Jennifer L. Herold of Texas A&M Health Science Center and their colleagues took a closer look at the relationship between the bacteria and colorectal cancer. They found that the bacteria's presence is not coincidental — it is an active participant in promoting cancer cell growth and contributes to the development of colorectal cancer. Their findings were published July 13 in PLOS Pathogen.

Colorectal Cancer

Of all cancers, colorectal cancer is the second most likely (1.82% risk of dying from it) to kill any given person. Lung (5.31% risk) took first, and breast cancer (1.38% risk) took third. .

Colorectal cancer often begins as a polyp — a growth of tissue that forms on the inner wall of the colon or rectum. There are many types of colon polyps, and most are not cancerous. It can take up to 15 years for a polyp to develop into colorectal cancer. That's why early detection by colonoscopy or tests that detect blood hidden in feces is so important.

Colorectal adenocarcinoma

When detected early — before it has spread outside the colon — colorectal cancer has a 5-year survival rate of about 90%.

We've known that infection with the bacteria Streptococcus gallolyticus has been a consistent signal that a person will develop abnormal colon growths like colon adenomas — an abnormal growth of intestinal mucus-producing cells that can develop into cancer — or cancers, for almost 40 years.

A previous review of scientific papers published between 1970 and 2010 found that patients with Streptococcus gallolyticus (know as Streptococcus bovis at that time) infections had about a 60% chance of also having colon adenomas or cancer.

And that's all we've known for decades — an observation that infection with the strep bacteria and colorectal cancer are somehow related — until Kumar and Herold found the connection.

Strep Is Not an Innocent Bystander

Working from the knowledge that infection with a subspecies of Streptococcus gallolyticus has been associated with a 7-fold higher risk of colorectal cancer for decades, the research team conducted some experiments to find out why.

They studied the bacteria using cultured human colorectal cells, mice with colorectal cancer, and tissue from human tumors. When researchers grew colorectal cells and Streptococcus gallolyticus together, the cancer cells increased in number, but only when the bacteria and the cells were in direct contact with each other. The substances secreted by the strep bacteria did not cause the growth of cancer cells. The bacteria themselves had to be present and in contact with the cells.

Detection of Sg (shown as individual red dots) in a human colon tumor.

Overproduction of a protein named ß-catenin plays a role in a pathway that leads to colorectal cancer. The scientists found that if they reduced ß-catenin in colorectal cancer cells that the bacteria did not cause the cancer cells to grow. When researchers injected mice with colorectal cancer with Streptococcus gallolyticus, they grew more tumors, bigger tumors, tumors with worse grades of cancer (more severe cancer), and made more ß-catenin than mice injected with a different type of bacteria as a control.

Analysis of 148 tumor samples and 128 samples of nearby tissue from patients with colorectal cancer showed that three-quarters of the tissues had Streptococcus gallolyticus bacteria in them, mostly in the tumor tissue samples.

"A bacterium that has been well documented to have a strong clinical association with colorectal cancer is now found to also functionally promote the development of colorectal cancer," said Kumar in a press release.

The study authors say the next steps are to drill down to find the exact factors from the strep bacteria that cause cancer cells to grow. Then, they hope their findings can be used to develop new strategies to diagnose, prevent, and treat colorectal cancer.

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Cover image via Richard Facklam/CDC